POS1013 EARLY LOW DOSE IL-2 REDUCED THE INITIATION OF COLLAGEN-INDUCED ARTHRITIS THROUGH RESTORING TFH/TFR BALANCE
Authors: R. Su, B. C. LI, C. Wang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> To date,there are also exploratory studies of partial prevention of RA, including dexamethasone,methotrexate, hydroxychloroquine, abatacept and so on[1].But no interventions have been proven to prevent the clinical onset of RA, and only some drugs may delay the appearance of clinical symptoms. Early restoration of immune tolerance and interruption an autoimmune response that is not yet well established may help prevent the occurrence of RA or achieve drug-free remission.Low-dose IL-2 is a new therapeutic strategy for many autoimmune diseases, including RA.However, no studies have focused on its preventive effect in Pre-RA. <h3>Objectives</h3> The aim of this study was to observe the preventive effect of low-dose IL-2 in collagen-induced arthritis, and to characterize the cellular mechanism underlying such an effect. <h3>Methods</h3> CIA is induced by primary immunization of bovine type II collagen (CII) and complete Freund's adjuvan and a booster injection of CII in incomplete Freund's adjuvant (day 21)in DBA/1 mice. CIA mice were intraperitoneally injected with 30000 IU rhIL-2 every other day at 0, 7, 14 and 21 days after primary immunization, lasted for 28 days.In addition CIA control, healthy control and Control-IL-2 were set up.Arthritis index was assessed after booster immunization.At the end of the experiment(d56 after the initial immunization), splenic mononuclear detected by flow cytometry. <h3>Results</h3> (1)The results showed that incidence rate of arthritis of the 0d-IL-2 group was lower than the 7d, 14d, 21d and CIA model groups (p=0.0012, p=0.0003, p&lt;0.0001,p=0.0013). The arthritis index(AI) of 0d-IL-2 group was lower than that of 14d, 21d and CIA groups (p=0.0224, 0.0389, 0.0498), showing a trend of delayed arthritis.The AI of the 21d-IL-2 group had a decreased tendency compared with CIA group, but there was no significant difference. (2)At the end of the experiment, Flow cytometry was used to evaluate the proportions of Tfh(CD4<sup>+</sup>CXCR5<sup>+</sup>) and Tfr(CD4<sup>+</sup>CXCR5<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>) cells in spleen.The Tfh had no significant changes among all groups. The 14d-IL-2 group showed an increased trend of Tfh compared with other groups, but there was no statistical difference.The proportion of Tfr cells in both 0d-IL-2 and 14d-IL-2 group was significantly increased than that of CIA and healthy control group.By comparing the proportion of Tfh/Tfr in each group, the proportion of Tfh/Tfr in CIA group was significantly higher than healthy control group. Compared with CIA model group,Tfh/Tfr in all intervention groups (0d,7d,14d,21d-IL-2) were significantly lower. <h3>Conclusion</h3> Early administration of low-dose IL-2 may help reduce the incidence of arthritis and disease activity in CIA by restoring Tfh/Tfr balance,but it has time heterogeneity. <h3>References</h3> [1] Frazzei G, Musters A, de Vries N, et al. Prevention of rheumatoid arthritis: A systematic literature review of preventive strategies in at-risk individuals. Autoimmun Rev. 2022,22:103217. [2] Rosenzwajg M, Lorenzon R, Cacoub P, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019,78(2):209-217. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.